The purpose of the project described in this application is to analyze structural bases of B7:CD28/CTLA4 interactions and respective function of CD28 and CTLA4 in late phase of immune responses, namely clonal expansion and effector function of activated T cells. Specifically the following issues will be addressed: 1) Structural basis of B7:CD28/CTLA4 interaction. 2) The possibility of transduction of opposing biological signals by CD28 and CTLA4. 3) The effector function in anti-tumor immunity through the identification of the receptor involved in rejecting B7-bearing tumors in vivo and cytolysis of B7-bearing tumors in vitro. The experiments will employ site directed mutagenesis of B7-1 and the use of CD28 KO mice.